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| Status |
Public on Jan 09, 2008 |
| Title |
Gene expression response to the antifungal compound sampangine in S. cerevisiae |
| Organism |
Saccharomyces cerevisiae |
| Experiment type |
Expression profiling by array
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| Summary |
Sampangine, a plant-derived alkaloid found in the Annonaceae family, exhibits strong inhibitory activity against the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In the present study, transcriptional profiling experiments coupled with the analysis of mutants were performed in an effort to elucidate its mechanism of action. Using Saccharomyces cerevisiae as a model organism, we show that sampangine produces a transcriptional response indicative of hypoxia, altering the expression of genes known to respond to low oxygen conditions. Several additional lines of evidence obtained suggest that these responses could involve effects on heme. First, the hem1 deletion mutant lacking the first enzyme in the heme biosynthetic pathway showed increased sensitivity to sampangine, and exogenously supplied hemin partially rescued the inhibitory activity of sampangine in wild-type cells. In addition, heterozygous mutants with deletions in genes involved in five out of eight steps in the heme biosynthetic pathway showed increased susceptibility to sampangine. Furthermore, spectral analysis of pyridine extracts indicated significant accumulation of free porphyrins in sampangine-treated cells. Transcriptional profiling experiments were also performed in C. albicans to investigate the response of a pathogenic fungal species to sampangine. Taking into account the known differences in the physiological responses of C. albicans and S. cerevisiae to low oxygen, significant correlations were observed between the two transcription profiles suggestive of heme-related defects. Our results indicate that the antifungal activity of the plant alkaloid sampangine is due, at least in part, to perturbations in the biosynthesis or metabolism of heme.
Keywords: antifungal compound, transcriptional profiling, S. cerevisiae
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| Overall design |
S. cerevisiae S288C cells at OD 0.2 were treated with either sampangine (SMP) at IC50 concentration (1.17 ug/ml), or solvent (0.25% DMSO), allowed to grow to OD 0.5, then harvested and frozen. Three biological replicate samples were analyzed for each treatment.
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| Contributor(s) |
Agarwal AK, Xu T, Jacob MR, Feng Q, Lorenz MC, Walker LA, Clark AM |
| Citation(s) |
18156292 |
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| Submission date |
Jan 05, 2008 |
| Last update date |
Jul 01, 2016 |
| Contact name |
Ameeta Agarwal |
| E-mail(s) |
aagarwal@olemiss.edu
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| Phone |
662-915-1218
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| Organization name |
University of Mississippi
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| Department |
National Center for Natural Products Research
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| Street address |
NCNPR, Room 2049
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| City |
University |
| State/province |
MS |
| ZIP/Postal code |
38677 |
| Country |
USA |
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| Platforms (1) |
| GPL90 |
[YG_S98] Affymetrix Yeast Genome S98 Array |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE10104 |
Gene expression response to the antifungal compound sampangine |
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| Relations |
| BioProject |
PRJNA108961 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10073_RAW.tar |
7.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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